A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb

Abstract

AbstractChimeric antigen receptor T-cell immunotherapy (CAR-T) has shown remarkable efficacy in treating tumors of lymphopoietic origin. Herein, we demonstrate an effective CAR-T cell treatment for recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL) has been demonstrated. The extracellular fragment gene sequences of CD30 were obtained from tumor tissues of PTCL patients and cloned into a plasmid vector to express the CD30 antigen. The CD30 targeting single-chain antibody fragment (scFv) was obtained from CD30-positive monoclonal hybridoma cells, which were obtained from CD30 antigen immunized mice. After a second-generation of CAR lentiviral construction, CD30 CAR T cells were produced and used to determine the cytotoxicity of this construct toward Karpas 299 cells. The results of CD30 CAR T-mediated cell lysis show that 9C11-2 CAR T cells could significantly promote the lysis of CD30-positive Karpas 299 cells in both LDH and real-time cell electronic sensing (RTCA) assays. In vivo data show that 9C11-2 CAR T cells effectively suppress the tumor growth in a Karpas 299 cell xenograft NCG mouse model. The CD30 CAR T cells exhibited an efficient cytotoxic effect after being co-cultured with the target cells and they also exhibited a significant tumor-inhibiting ability after being intravenously injected into PTCL xenograft tumors; these observations suggest that the new CD30 CAR-T cell may be a promising therapeutic candidate for cancer therapy.